Tumor-associated macrophages (TAM) are abundant in many types of cancers. Together with other stromal[unreadable] cell types (fibroblasts, neutrophils, mast cells, T cells, dendritic cells, endothelial cells) and matrix[unreadable] components (collagen, fibronectin, glycoproteins) these cells exhibit complex regulatory functions mediated[unreadable] through growth factors, chemokines, cytokines and angiogenesis promoting factors. There is compelling[unreadable] evidence that TAM respond to tumor stimuli with the release of proteolytic enzymes, chemokines, cytokines[unreadable] and growth factors and have therefore been proposed to be essential to invasion, proliferation, angiogenesis[unreadable] and metastases formation. Recent advances in in vivo imaging have yielded new insights into migration of[unreadable] host and cancer cells, however the necessary tools to fully quantify and catalog these interactions are still[unreadable] largely missing. The overall goal of this project is therefore to develop novel in vivo imaging agents with[unreadable] specificity for subtypes of TAM, their monocytic precursors and tissue macrophages. This will be done using[unreadable] powerful library approaches and recently developed nanomaterials capable of detection by multiple imaging[unreadable] modalities and spatial resolutions. In parallel, we will continue the development of imaging agents for other[unreadable] stromal cells ((myo)fibroblasts, NK cells and T cells) to be used in the Weinberg and Jacks projects. In[unreadable] collaboration with the Hynes group as well as other macrophage research groups, we will study the[unreadable] recruitment and fate of monocytes/macrophages in tumors. Finally, targeting TAM as a therapeutic strategy[unreadable] against cancer is an intriguing concept that needs further study. We will therefore measure the effect on[unreadable] tumor growth and metastatic potential following selective anti-TAM therapy. Specifically, we will ask the[unreadable] following questions: 1) What is(are) the direct precursor(s) of TAM, and is there differential participation of[unreadable] TAM subsets in primary and metastatic tumors? 2) What is the involvement of TAM during tumor progression[unreadable] (initiation, invasion, angiogenesis and metastasis)? 3) Does elimination of distinct TAM subsets result in[unreadable] measurable anti-cancer effects? The developed agents and strategies will be designed to be clinically[unreadable] translatable and should support our previous clinical data in glioma that imaging of TAM can have important[unreadable] prognostic and therapeutic implications.